KR101585028B1

KR101585028B1 - Polymer coated stent for treatment of aneurysm and manufacturing method of the same

Info

Publication number: KR101585028B1
Application number: KR1020150077613A
Authority: KR
Inventors: 김한기; 유현승; 서준혁; 박준규; 송석범; 금창헌; 조재화; 진규현; 이덕희; 황선문; 김태일; 임옥균; 이가영; 박찬희
Original assignee: (주)시지바이오; 재단법인 아산사회복지재단; 전북대학교산학협력단
Priority date: 2015-06-01
Filing date: 2015-06-01
Publication date: 2016-01-14

Abstract

The present invention relates to a polymer-coated stent for the treatment of an aneurysm comprising a polymer fiber layer formed by electrospinning on a stent, and a method of manufacturing the same.

Description

TECHNICAL FIELD [0001] The present invention relates to a polymer coated stent for treating an aneurysm, and a method for manufacturing the same. [0002]

A blood vessel is a tube that circulates blood throughout the body and is made up of an artery, a capillary, and a vein, which are interconnected to various parts of the body and the end of the body. Lt; / RTI >

These blood vessels may be obstructed, stenosed, ruptured by aneurysm that locally dilates the vessel wall, and bleeding due to disease or other diseases. If these symptoms persist, the blood flow may be blocked or the flow of blood flow due to internal bleeding may not be smooth, resulting in paralysis or organ damage and life threatening.

In particular, cerebrovascular disease refers to a disorder in which blood vessels supplying blood to the brain are referred to. It causes local neurological symptoms such as loss of consciousness, hemiplegia, and speech disorders caused by sudden cerebral blood flow disorders. In severe cases, death It is a terrible disease that causes.

The brain aneurysm, a type of cerebrovascular disease, is an abnormally swollen part of the cerebral blood vessel wall. If a temporary high blood pressure is applied to the swollen blood vessel wall, the blood vessel wall ruptures and causes cerebral hemorrhage.

If these symptoms of cerebrovascular disease become worse, surgical operation is needed. However, surgery has a high mortality rate and has a long recovery period after surgery.

Recently, various methods for treating cerebrovascular diseases have been developed by non - surgical methods. Among them, there is a treatment method of inserting a stent, which is a prosthetic insert which can expand, reinforce, and prevent bleeding, while observing the blood vessel using a ray that can be seen through the inside of the human body such as X-rays and gamma rays.

In particular, stent implantation has been clinically proven in the treatment of cerebral vascular stenosis and cerebral aneurysm, and in the long term, it has been replaced by surgery, It is a technology that is expected to develop by replacing surgical procedures for the treatment of various diseases.

Currently, cylindrical stents and platinum coils (embolization) are used for the treatment of cerebral aneurysms. For example, Korean Patent No. 1300437 discloses a vascular stent for an aneurysm. However, since coil embolization inserts the stent together with the platinum coil to prevent the deviation of the platinum coil, the procedure time is long and the patient is burdened in cost. A stent for the treatment of a cerebral aneurysm that does not require a coil has been developed. A conventional stent for the treatment of an aneurysm has a full-covered stent and a blood flow to the cerebral aneurysm But it is difficult to use it clinically because it blocks the blood flow toward the branch blood vessel. In addition, the price was high and the shortening was so large that it was difficult to perform the procedure at the correct position.

In addition, a variety of stents for the treatment of aneurysms have been developed, but they have also blocked the blood flow to the branch vessels, not only the aneurysm, but also excessively thick, bulky, inflexible, and low mechanical strength of the membrane on the surface of the stent.

Therefore, it is necessary to develop a stent for the treatment of aneurysm that can effectively block blood flow to an aneurysm rather than a branch vessel, while economizing and shortening the procedure time without requiring coil embolization.

Conventionally, coil embolization has been performed in which a platinum coil is inserted into an aneurysm and a cylindrical stent is inserted into a blood vessel for fixation of the platinum coil. However, in the case of coil embolization, the platinum coil used is expensive, and because the insertion of the coil and the insertion of the stent must be performed at the same time, the procedure time is long and the operator is burdened.

The stent for the treatment of aneurysms, which does not require a coil, is also coated on the entire surface of the stent wall so that blood does not pass through the stent wall. Therefore, when the stent is inserted into the blood vessel, the blood flow to the branch vessel is blocked not only by the aneurysm.

The present invention has been made to solve the above-mentioned problems of the prior art, and it is an object of the present invention to provide a stent for treating an aneurysm by forming a polymer fiber layer having a different pore size according to a position on a stent using gas- The stent wall at the site where the aneurysm was inserted at the site where the aneurysm was inserted did not pass through the bloodstream because the pore size was small. However, the stent wall at the site where the branch vessel was present had a large pore size, Coated stent and a method of manufacturing the same.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

As a technical means for achieving the above technical object, the first aspect of the present invention comprises a stent and a polymer fiber layer formed on the stent, wherein the polymer fiber layer includes a portion having a first average pore size, Coated stents for the treatment of aneurysms, which are formed by electrospinning.

Also according to one embodiment of the present invention, there is provided a stent comprising: a stent; And a polymer fiber layer formed on the stent, wherein the polymer fiber layer includes a first portion having a first average pore size and a second portion having a second average pore size, wherein the polymer fiber layer is formed by electrospinning Coated stents for the treatment of aneurysms.

According to an embodiment of the present invention, the first average pore size is smaller than the second average pore size, and when the polymer-coated stent is inserted into a blood vessel for treating an aneurysm, As shown in Fig.

According to one embodiment of the invention, the first average pore size may be from about 1 [mu] m to about 10 [mu] m.

According to one embodiment of the disclosure, the second average pore size may be from about 10 [mu] m to about 100 [mu] m.

According to one embodiment of the present disclosure, it may not include a separate occlusion device inserted into the aneurysm.

According to one embodiment of the disclosure, the stent may be a metal stent or a polymer stent.

According to an embodiment of the present invention, the polymer fiber layer may include a biodegradable polymer.

According to one embodiment of the present invention, the polymeric fibrous layer may be formed of a polymer selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly- D-lactic acid, poly-L-lactic acid-e-caprolactone copolymer (PLCL), polyurethane, polyethylene glycol, polyamino acid, polyanhydride, polyorthoester, polydioxanone, polyphosphagene, Cellulose acetate propionate, cellulose acetate butyrate, cellulose triacetate, and copolymers thereof.

According to an embodiment of the present invention, the polymer fiber layer may further contain an endothelial cell proliferation promoter.

According to a second aspect of the present invention, there is provided a method of forming a polymer fiber layer by electrospinning a polymer on a stent, wherein the electrospinning is gas guided electrospinning and the radial position of the polymer is controlled by the gas- Thereby forming a polymer fiber layer including a portion having a first average pore size on the stent. The present invention also provides a method of manufacturing a polymer-coated stent for treating an aneurysm.

According to one embodiment of the present disclosure, there is provided a method of forming a polymeric fibrous layer by electrospinning a polymer on a stent, the electrospinning being gas guided electrospinning, Forming a polymeric fibrous layer comprising a first portion having a first average pore size and a second portion having a second average pore size on the stent by adjusting the position of the first portion and the second portion of the stent, .

According to one embodiment of the disclosure, it may comprise spinning the polymer such that the first average pore size of the first portion is from about 1 [mu] m to about 10 [mu] m.

According to one embodiment of the disclosure, it may comprise spinning the polymer such that the second average pore size of the second portion is from about 10 [mu] m to about 100 [mu] m.

According to one embodiment of the present invention, forming a polymer fiber layer comprising a first portion having a first average pore size and a second portion having a second average pore size on the stent is performed by a single continuous process .

According to one embodiment, the polymer is selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly- , Polylactic acid, polylactic acid-e-caprolactone copolymer (PLCL), polyurethane, polyethylene glycol, polyamino acid, polyanhydride, polyorthoester, polydioxanone, polyphosphagene, cellulose Cellulose triacetate, and copolymers thereof. [0043] The term " a "

The above-described task solution is merely exemplary and should not be construed as limiting the present invention. In addition to the exemplary implementations described above, there may be additional implementations and embodiments described in the drawings and detailed description of the invention.

According to the above-mentioned problem solving means, since the polymer fiber layer including the portion having the first average pore size is formed on the stent, it is possible to block only the blood flow to the aneurysm except the branch vessel without requiring coil embolization A polymer coated stent for treating an aneurysm can be provided.

The present invention relates to a method of forming a polymeric fiber layer on a stent comprising a first portion having a first average pore size and a second portion having a second average pore size to thereby elastically select and block blood flow to an aneurysm except a branch vessel A polymer coated stent for treating an aneurysm can be provided.

The polymer coated stent for the treatment of an aneurysm of the present invention is formed by forming a polymer fiber layer on a stent by gas induced electrospinning and includes spinning a polymer fiber by electrospinning on the same stent, The thickness of the polymer fiber layer formed on the stent and the size of the pores can be adjusted.

That is, when the stent is inserted into the blood vessel for the treatment of the aneurysm, the polymer fiber layer is formed more closely in the portion where the aneurysm is located, so that the pore size is controlled to be small enough to prevent passage of blood flow. The pore size can be largely controlled so that blood flow can easily pass through by forming the polymer fiber layer.

In addition, the polymer fiber layer formed by the electrospinning method is excellent in physical properties such as strength and flexibility, has a low possibility of occurrence of fistula, and has a more stable advantage in living body transplantation. In addition, since it is not necessary to use a plurality of membranes overlaid, a thinner and more flexible stent can be manufactured. In addition, since the polymer fiber layer formed by electrospinning has a fabric shape, it can induce endothelial cell proliferation and induce quick re-endothelialization compared with a simple film type membrane.

Moreover, since the polymer fiber layer having different pore sizes on the same stent can be formed by a single continuous process, it is possible to economically and quickly produce the entire thickness of the stent while keeping it unnecessarily thick.

FIG. 1 is a schematic view of a polymer-coated stent for treating an aneurysm of the present invention inserted into a blood vessel formed with an aneurysm.
2 is a scanning electron microscope (SEM) image of a polymer coated stent for treating an aneurysm according to an embodiment of the present invention.
FIG. 3 is a schematic diagram of a gas-induced electrospinning system for use in a method of manufacturing a polymer-coated stent for treating an aneurysm in accordance with an embodiment of the present invention.
FIG. 4 is an image showing selective blocking of blood flow by inserting a polymer coated stent for treating an aneurysm into a vein of a pig according to an embodiment of the present invention.
FIG. 5 is an image of H & E staining and fibrin staining after collection of a polymer coated stent for the treatment of an aneurysm in pig blood vessels 4 weeks later according to one embodiment of the present invention.
6 is an image obtained by measuring the particle image velocity by inserting the stent according to one comparative example of the present application into an aneurysm model.
FIG. 7 is an image obtained by measuring the particle image velocity by inserting the stent according to one comparative example of the present application into an aneurysm model.
FIG. 8 is an image obtained by measuring the particle image velocity by inserting the stent according to an embodiment of the present invention into an aneurysm model.
FIG. 9 is a graph showing numerical results of a particle image velocity measurement analysis by inserting a stent according to an embodiment of the present invention into an aneurysm model.
10 is a schematic diagram of a particle image velocity measurement system used in one embodiment of the present application.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when a part is referred to as being "connected" to another part, it is not limited to a case where it is "directly connected" but also includes the case where it is "electrically connected" do.

Throughout this specification, when a member is " on " another member, it includes not only when the member is in contact with the other member, but also when there is another member between the two members.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

The terms "about "," substantially ", etc. used to the extent that they are used throughout the specification are intended to be taken to mean the approximation of the manufacturing and material tolerances inherent in the stated sense, Accurate or absolute numbers are used to help prevent unauthorized exploitation by unauthorized intruders of the referenced disclosure. The word " step (or step) "or" step "used to the extent that it is used throughout the specification does not mean" step for.

Throughout this specification, the term "combination thereof" included in the expression of the machine form means one or more combinations or combinations selected from the group consisting of the constituents described in the expression of the machine form, And the like.

Throughout this specification, the description of "A and / or B" means "A, B, or A and B".

Hereinafter, a polymer-coated stent for treating an aneurysm of the present invention and a method of manufacturing the same will be described in detail with reference to embodiments, examples and drawings. However, the present invention is not limited to these embodiments and examples and drawings.

According to a first aspect of the present invention, there is provided a stent comprising a stent and a polymer fiber layer formed on the stent, wherein the polymer fiber layer includes a portion having a first average pore size, and the polymer fiber layer is formed by electrospinning A polymer-coated stent for use in the present invention can be provided. At this time, the present invention can be formed to include a polymer fiber layer only in a part of the stent. For example, the stent of the present invention may be formed to include the polymer fiber layer only in the central region.

According to an embodiment of the present invention, the polymer fiber layer includes a first portion having the first average pore size and a second portion having the second average pore size, wherein the first average pore size is smaller than the second average pore size Wherein the polymer coated stent is inserted such that the first portion is positioned at an aneurysm occurrence site of the blood vessel when inserted into a blood vessel for treatment of an aneurysm. But may not be limited thereto.

The present invention relates to a stent; And a polymer fiber layer formed on the stent, wherein the polymer fiber layer includes a first portion having a first average pore size and a second portion having a second average pore size, wherein the polymer fiber layer is formed by electrospinning Coated stents for the treatment of aneurysms.

The polymer coated stent for treating an aneurysm has a polymer fiber layer coated on a stent, and the polymer fiber layer is formed into a fabric shape by electrospinning to have nano-sized pores. The polymer fiber layer on the polymer-coated stent for treating the aneurysm may have a second average pore size, and the second average pore size corresponds to a pore size of the bloodstream.

However, when the polymer-coated stent for treating an aneurysm is placed in a blood vessel for treatment of an aneurysm, the polymer fiber layer in contact with the aneurysm is made to have a first average pore size. Since the first average pore size has a small pore size so that the blood flow can not freely flow, the blood flow passing through the inside of the stent can not pass through the first portion having the first average pore size. Therefore, the aneurysm isolated from the blood flow by the first portion having the first average pore size is separated from the normal blood flow, so that the rupture of the aneurysm and the risk thereof can be prevented.

For example, polymer coated stents for the treatment of aneurysms can be used for the treatment of cerebral aneurysms.

The use of a polymer-coated stent for the treatment of aneurysms in this case selectively regulates the pore size of the polymer fiber layer to selectively block blood supply to the abnormally swollen aneurysm of the aneurysm, It can be stably blocked. Therefore, it is possible to prevent the rupture of the cerebral aneurysm due to an increase in blood pressure, and at the same time, it is possible to supply blood to branch vessels, thereby enabling selective blood flow cutoff and supply. If the blood supply to the aneurysm is blocked, the aneurysm of the cerebral aneurysm may slowly coagulate and become necrotic and disappear.

In addition, the pore size of the polymer fiber layer coated on the stent can be further subdivided and adjusted to produce the third or more different segments in addition to the first and second portions. The various segments can each be adjusted to have different average pore sizes. In addition, when the stent is installed at a desired position, it can be removed again so that the position can be changed even after the stent is installed.

1 is a schematic view of a polymer coated stent for treating an aneurysm of the present invention inserted into a blood vessel. 1, a polymer coated stent 100 for treating an aneurysm of the present invention is inserted into a blood vessel 210 in which an aneurysm 230 is formed. The stent includes a first portion 110 And a second portion 130 that is not coated with a polymer.

1, a polymer-coated stent 100 for treating an aneurysm of the present invention is inserted into a blood vessel 210 in which a pulsation 230 is formed, and the stent has a relatively small pore A first portion 110 having a relatively large pore size and a second portion 130 having a relatively large pore size.

Since the first portion 110 has small pores that the blood flow can not easily pass through, the blood can not be supplied into the aneurysm 230, so that the aneurysm may slowly coagulate and necrotize with time. Because the second portion 130 has pores that are large enough to allow blood flow to pass easily, it does not block blood flow to the branch vessels that are present other than the aneurysmal portion.

Figure 2 shows a scanning electron microscope (SEM) image of a polymeric fiber layer coated on a stent, according to one embodiment of the present invention.

The thickness of the polymeric fiber layer formed on the stent of the present invention can be easily adjusted by controlling the electrospinning process according to the intention of the user or the purpose of treatment according to methods well known in the art.

For example, the electrospinning method may be performed by a stent coating apparatus disclosed in Korean Patent No. 1374073. An exemplary schematic diagram of an electrospinning system is shown in FIG.

For example, the stent may be a tubular structure in which filaments are woven, but may not be limited thereto. For example, the stent may be a tubular structure in which filaments are folded in a zigzag shape and wound in a cylindrical shape, but the present invention is not limited thereto. For example, the stent may be a reticulated or latticed tube stent, but not limited thereto, any stent used in the art can be used. For example, the stent may be, but is not limited to, a wire weave stent or a laser-cut stent. For example, the cross section of the filament may be circular or elliptical, but may not be limited thereto.

For example, the diameter of the filaments making up the stent may range from about 0.01 mm to about 0.4 mm, such as from about 0.01 mm to about 0.3 mm, from about 0.01 mm to about 0.2 mm, from about 0.01 mm to about 0.1 mm, From about 0.01 mm to about 0.05 mm, from about 0.01 mm to about 0.03 mm, from about 0.03 mm to about 0.4 mm, from about 0.05 mm to about 0.4 mm, from about 0.1 mm to about 0.4 mm, from about 0.2 mm to about 0.4 mm, mm to about 0.4 mm, but may not be limited thereto.

For example, the outer diameter of the stent may range from about 0.1 mm to about 7 mm, such as from about 0.1 mm to about 5 mm, from about 0.1 mm to about 2 mm, from about 0.1 mm to about 1 mm, from about 0.1 mm to about From about 0.5 mm to about 7 mm, from about 0.7 mm to about 7 mm, from about 1 mm to about 7 mm, from about 3 mm to about 7 mm, or from about 5 mm to about 7 mm, mm, but may not be limited thereto.

According to an embodiment of the present invention, the first average pore size is smaller than the second average pore size, and when the polymer-coated stent is inserted into a blood vessel for treating an aneurysm, But the present invention is not limited thereto.

According to one embodiment of the present invention, the first average pore size may be from about 1 [mu] m to about 10 [mu] m, but is not limited thereto. For example, the first average pore size may be from about 1 μm to about 9 μm, from about 1 μm to about 8 μm, from about 1 μm to about 7 μm, from about 1 μm to about 6 μm, from about 1 μm to about 5 μm From about 1 μm to about 4 μm, from about 1 μm to about 3 μm, from about 1 μm to about 2 μm, from about 2 μm to about 10 μm, from about 3 μm to about 10 μm, from about 4 μm to about 10 μm, But may not be limited to, from about 5 μm to about 10 μm, from about 6 μm to about 10 μm, from about 7 μm to about 10 μm, from about 8 μm to about 10 μm, or from about 9 μm to about 10 μm.

According to one embodiment of the invention, the second average pore size may be from about 10 [mu] m to about 100 [mu] m, but is not limited thereto. For example, the second average pore size may be from about 10 袖 m to about 90 袖 m, from about 10 袖 m to about 80 袖 m, from about 10 袖 m to about 70 袖 m, from about 10 袖 m to about 60 袖 m, From about 10 μm to about 40 μm, from about 10 μm to about 30 μm, from about 10 μm to about 20 μm, from about 20 μm to about 100 μm, from about 30 μm to about 100 μm, from about 40 μm to about 100 μm, From about 50 탆 to about 100 탆, from about 60 탆 to about 100 탆, from about 70 탆 to about 100 탆, from about 80 탆 to about 100 탆, from about 90 탆 to about 100 탆, or about 10 탆, .

The average pore size can be measured by a pore size measurement method commonly used in the art. For example, the average pore size may be measured using an Image J program, but may not be limited thereto.

According to one embodiment of the present disclosure, it may not include, but is not limited to, a separate occlusion device inserted into the aneurysm.

When using the polymer coated stent for treating an aneurysm of the present invention, blood flow to an aneurysm can be blocked without an occlusion device such as a platinum coil inserted into the aneurysm. Therefore, it is possible to exhibit an advantageous effect of treating an aneurysm without the need for a separate occlusion device.

According to an embodiment of the present invention, the stent may be a metal stent or a polymer stent, but the present invention is not limited thereto.

For example, the polymer stent may include, but is not limited to, a biodegradable polymer. For example, the biodegradable polymer may be selected from the group consisting of polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly-D-lactic acid, poly- L-lactic acid-e-caprolactone copolymer (PLCL), polyurethane, polyethylene glycol, polyamino acid, polyanhydride, polyorthoester, polydioxanone, polyphosphagene, cellulose acetate butyrate, cellulose triacetate And copolymers thereof, but may not be limited thereto.

For example, the metal stent may include one or more selected from the group consisting of stainless steel, nickel, titanium, chromium, cobalt, magnesium, platinum, tantalum, nitinol, gold, silver and alloys thereof. But may not be limited.

According to one embodiment of the present invention, the polymer fiber layer may include, but is not limited to, a biodegradable polymer.

For example, the biodegradable polymer may include a polymeric material commonly used in biodegradable stents or biodegradable coatings in the art.

For example, the polymeric fibrous layer may be applied for about 1 to 10 months, about 2 to 10 months, about 3 to 10 months, about 4 to 10 months, about 2 to 10 months, About 4 to 10 months, about 6 to 10 months, about 8 to 10 months, about 1 to 8 months, about 1 to 6 months, about 1 to 4 months, about 1 to 2 months, But may be, but not limited to, complete degradation in vivo within about 1 to 4 weeks, about 1 to 3 weeks, about 1 to 2 weeks, or about 4 weeks.

According to one embodiment of the present invention, the polymeric fibrous layer may be formed of a polymer selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly- D-lactic acid, poly-L-lactic acid-e-caprolactone copolymer (PLCL), polyethylene glycol, polyamino acid, polyanhydride, polyorthoester, polydioxanone, polyphosphagene, cellulose acetate butyl But is not limited to, one or more selected from the group consisting of cellulose triacetate, cellulose triacetate, and copolymers thereof.

According to one embodiment of the present invention, the polymer fiber layer may further contain an endothelial cell proliferation promoter, but may not be limited thereto. For example, the endothelial cell proliferation promoter may be mixed with a polymer and electrospun, or may be coated after a polymer fiber layer is formed on a stent. If the endothelial cell proliferation promoter is further contained in the polymer fiber layer, it may be more effective in the treatment of an aneurysm.

Although a detailed description of the parts overlapping with the first aspect of the present application is omitted, the description of the first aspect of the present application may be applied to the second aspect of the present invention.

For example, the electrospinning may be performed by a stent coating apparatus disclosed in Korean Patent No. 1374073.

For example, the gas-induced electrospinning may be with an electrospinning system to which a gas-guided nozzle is applied. The gas-guiding nozzle applies nitrogen or air around the nanofibers emitted from the nozzle to adjust the direction of the nanofibers.

According to the method of the present invention, since the polymer fiber layer having different pore sizes on the same stent can be formed in a single continuous process, economical and rapid production is possible while keeping the overall thickness of the stent unnecessarily large.

When the polymer fiber layer is formed on the stent by gas-induced electrospinning according to the method of the present invention, the polymer fibers are radiated on the stent to form a coating layer in the form of a fabric, and the coating layer has nano-sized pores . The stent of the present invention is basically formed to have a second average pore size, and the second average pore size may correspond to a pore size of the blood flow. In this case, the second average pore size may mean a metal stent or a polymer stent in which the polymer fiber layer is not coated. The polymeric fibrous layer on the stent is basically formed so as to have a second average pore size, and the second average pore size may correspond to a pore size such that the blood flow can freely flow.

However, when the polymer-coated stent for treating an aneurysm is placed in a blood vessel for treatment of an aneurysm, the polymer fiber layer in contact with the aneurysm is formed to have a first average pore size. Since the first average pore size has a small pore size so that the blood flow can not freely flow, the blood flow passing through the inside of the stent can not pass through the first portion having the first average pore size. Therefore, the aneurysm isolated from the blood flow by the first portion having the first average pore size is separated from the normal blood flow, so that the rupture of the aneurysm and the risk thereof can be prevented.

According to the method of manufacturing a polymer-coated stent for treating an aneurysm of the present invention, it is possible to manufacture the third part or more various segments other than the first part and the second part by further finely controlling the pore size of the polymer fiber layer coated on the stent have. The various segments can each be adjusted to have different average pore sizes. In addition, when the stent is installed at a desired position, it can be removed again so that the position can be changed even after the stent is installed.

According to one embodiment of the disclosure, it may include, but is not limited to, spinning the polymer such that the first average pore size of the first portion is from about 1 μm to about 10 μm.

According to one embodiment of the present disclosure, it may include, but is not limited to, spinning the polymer such that the second average pore size of the second portion is from about 10 μm to about 100 μm.

According to one embodiment of the present invention, forming a polymer fiber layer comprising a first portion having a first average pore size and a second portion having a second average pore size on the stent is performed by a single continuous process But may not be limited thereto.

According to one embodiment, the polymer is selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly- , Polylactic acid, poly-L-lactic acid-e-caprolactone copolymer (PLCL), polyethylene glycol, polyamino acids, polyanhydrides, polyorthoesters, polydioxanone, polyphosphagene, cellulose acetate butyrate , Cellulose triacetate, and copolymers thereof, but may not be limited thereto.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[ Example ]

Polymer coating for the treatment of aneurysms Stent pig Intravascular transplantation

In order to confirm the selective blood flow blocking ability of the polymer coated stent for treating an aneurysm of the present invention, a stent was inserted into the blood vessel of the pig to observe the blocking of blood flow (FIG. 4).

1) Set up an experimental animal model

Animal model experiments and preclinical animal experiments were conducted under the approval of the Ethics Committee of the Institute of Clinical Research. Experimental animals were fed 30 ~ 35kg of sows in mini pigs one week before the experiment. All pigs received daily 100 mg of aspirin and 75 mg of clopidogrel daily for the first week of the experiment.

2) Stent insertion method

Pigs were anesthetized by intramuscular injection of 12 mg / kg of ketamine and 8 mg / kg of xylazine. The experimental pigs were fasted the night before, and 2% lidocaine was injected under the aseptic condition at the incision site and the carotid artery was incised and a 7 French artery sheath was inserted.

10,000 units of heparin sodium was administered through the carotid artery, and a 7 French coronary artery guiding catheter was placed in the femoral artery under the guidance of a C-arm (Philips BV 25 Gold).

During the experiment, oxygen was continuously supplied to the pigs using a facial oxygen mask, saline was supplied through the ear vein, and anesthesia was maintained by intravenous injection of midazolam.

The covered cerebral artery stent was transplanted into the left and right femoral arteries with branch vessels and transplanted so that the flow of blood into the branch vessels was blocked. After stenting, the carotid artery of the pig was ligated, and the skin of the neck was sutured and observed for 4 weeks by the animal breeder.

3) Evaluation of animal experimental results

Four weeks after placement of the stent, contrast agent was injected into the femoral artery to which the stent was implanted. After 4 weeks of stent placement, the stents were harvested and anatomical and pathological evaluations were performed. Specifically, the stent was transversely cut and quantitatively analyzed by H & E staining, Carstair's staining, fibrin staining, restenosis degree, thrombosis, inflammation score, etc. (Fig. 5). The tent was cut longitudinally and scanned by scanning electron microscope The state of the vascular tissues and the pattern of tissue changes were confirmed.

4) Results of animal experiments

It was confirmed that the blood supply to the branch vessel was blocked after the covered stent procedure (Fig. 4), and it was confirmed that the supply of blood to the site where the aneurysm occurred could be blocked. There was no adverse reaction or death in the pigs treated, and tissue analysis showed low inflammation and fibrin levels (FIG. 5).

Polymer coating for the treatment of aneurysms The stent Used Particle image velocity measurement (Particle Image Velocimetry , PIV ) analysis

In order to indirectly determine whether the blood flow can be selectively transmitted by appropriately adjusting the average pore size of the polymer coated stent for treating an aneurysm of the present invention, particle image velocity measurement analysis was performed. In the particle image velocity measurement analysis, the flow and velocity of the fluid in the aneurysm blood vessel model were analyzed by including tracer particles in the fluid flowing in the aneurysm blood vessel model and sensing the particles. A schematic diagram of the particle image velocity measurement and analysis system in this embodiment is shown in Fig.

In the in vitro model, a 4 mm diameter pipe was used as the maternal blood vessel model and a 10 mm diameter sphere was used as the aneurysm model. The experimental flow conditions were flow velocity of 480 ml / min, dynamic viscosity of 4.73 [mPa * s] at 17 ℃, and Reynolds number of 663, realizing a Poiseuille flow in normal flow.

Fluid flow in the vascular model was visualized by detecting tracer particles in the fluid using a 1 mm thick laser. Movement of the particles was detected by a local correlated continuous image recorded by a CCD camera. The cross-correlation function of the two samples was calculated using the FFT technique. Thus, the velocity of the fluid was measured at several points in the cross section of each sample at the same time and shown as an image (Figs. 6 to 8).

FIG. 6 is a schematic view of an aneurysm model in which a stent is not inserted, FIG. 7 is an aneurysm model inserted with a commonly used blood vessel stent, and FIG. As shown in FIG. In addition, the maximum velocity of the fluid in these models was measured and shown graphically in FIG.

According to FIGS. 6 to 9, when a completely covered stent is inserted into the polymer fiber layer formed by electrospinning, fluid flow into the aneurysm model is almost completely blocked. Thus, by using the stent of the present invention, blood flow into the aneurysm is blocked, It was confirmed that treatment would be possible.

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed in a similar fashion may also be implemented.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims

Stent; And
And a polymer fiber layer formed on the stent,
Wherein the polymer fiber layer has a first average pore size and includes a first portion corresponding to an aneurysm generating portion, the portion of the polymer fiber layer that is not the first portion is a second portion, Take the size,
Wherein the first average pore size is smaller than the second average pore size, the polymer fiber layer is formed by electrospinning,
Wherein the polymer-coated stent is inserted such that when the polymer-coated stent is inserted into a blood vessel for the treatment of an aneurysm, the first portion is located at the aneurcombotic region of the blood vessel.

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The method according to claim 1,
Wherein the first average pore size is between 1 μm and 10 μm.

The method according to claim 1,
Wherein the second average pore size is between 10 [mu] m and 100 [mu] m.

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The method according to claim 1,
Wherein the stent is a metal stent or a polymeric stent.

The method according to claim 1,
Wherein the polymer fiber layer comprises a biodegradable polymer.

The method according to claim 1,
The polymeric fibrous layer may be formed of at least one selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly- L-lactic acid-e-caprolactone copolymer (PLCL), polyurethane, polyethylene glycol, polyamino acid, polyanhydride, polyorthoester, polydioxanone, polyphosphagene, cellulose acetate butyrate, cellulose triacetate And a copolymer thereof. The polymer-coated stent for treating an aneurysm is not particularly limited.

The method according to claim 1,
Wherein the polymeric fibrous layer further comprises an endothelial cell proliferation promoter.

A method of forming a polymer fiber layer by electrospinning a polymer on a stent,
Wherein the electrospinning is gas guided electrospinning and the first portion having a first average pore size and the second portion having a second average pore size on the stent by controlling the radial position of the polymer by the gas- 2 < / RTI > part of the polymeric fiber layer,
Wherein the first portion is formed at a location corresponding to the aneurysm generating portion, and the second portion is formed at a location other than the first portion.

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11. The method of claim 10,
The polymer is radiated so that the first average pore size of the first portion is 1 to 10 [mu] m,
Wherein the polymer is radiated so that the second average pore size of the second portion is between 10 μm and 100 μm.

11. The method of claim 10,
Coated polymeric stent for the treatment of an aneurysm, wherein forming a polymeric fiber layer comprising a first portion having a first average pore size and a second portion having a second average pore size on the stent is performed by a single continuous process. &Lt; / RTI >

11. The method of claim 10,
The polymer may be selected from the group consisting of silicone, polycaprolactone, polylactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, poly-L-lactic acid, poly-D-lactic acid, poly- (PLCL), polyurethanes, polyethylene glycols, polyamino acids, polyanhydrides, polyorthoesters, polydioxanone, polyphosphogens, cellulose acetate butyrate, cellulose triacetate and cellulose triacetate And a copolymer thereof. The method of producing a polymer-coated stent for the treatment of an aneurysm is also provided.